Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

Journal	Biomaterials 284:121491 (2022)
Title	Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus
Laboratory	Laboratory of Tissue Biochemistry〈Prof. TSUMAKI Noriyuki〉

Abstract

The loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain. Here, we demonstrate that the implantation of human iPS cell-derived cartilaginous tissue (hiPS-Cart) restores this loss by replacing lost NP spatially and functionally. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. Single cell RNA sequencing (scRNA-seq) analysis revealed that cells in hiPS-Cart corresponded to chondrocyte-like NP cells but not to notochordal NP cells. The implantation of hiPS-Cart into a nuclectomized space of IVD in nude rats prevented the degeneration of the IVD and preserved its mechanical properties. hiPS-Cart survived and occupied the nuclectomized space for at least six months after implantation, indicating spatial and functional replacement of lost NP by hiPS-Cart. Further scRNA-seq analysis revealed that hiPS-Cart cells changed their profile after implantation, differentiating into two lineages that are metabolically distinct from each other. However, post-implanted hiPS-Cart cells corresponded to chondrocyte-like NP cells only and did not develop into notochordal NP cells, suggesting that chondrocyte-like NP cells are nearly sufficient for NP function. The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.

Authors	Takashi Kamatani (1, 2), Hiroki Hagizawa (1, 2, 7), Seido Yarimitsu (3), Miho Morioka (1, 7), Saeko Koyamatsu (1, 7), Michihiko Sugimoto (4), Joe Kodama (2), Junko Yamane (5), Hiroyuki Ishiguro (2), Shigeyuki Shichino (6), Kuniya Abe (4), Wataru Fujibuchi (5), Hiromichi Fujie (3), Takashi Kaito (2), Noriyuki Tsumaki (1, 7) Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.Department of Mechanical Systems Engineering, Faculty of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan. Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Research Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan. Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Building 17 Second Floor, 2641, Yamasaki, Noda, Chiba, 278-0042, Japan. Department of Tissue Biochemistry, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
PubMed	35395453

Authors

Takashi Kamatani (1, 2), Hiroki Hagizawa (1, 2, 7), Seido Yarimitsu (3), Miho Morioka (1, 7), Saeko Koyamatsu (1, 7), Michihiko Sugimoto (4), Joe Kodama (2), Junko Yamane (5), Hiroyuki Ishiguro (2), Shigeyuki Shichino (6), Kuniya Abe (4), Wataru Fujibuchi (5), Hiromichi Fujie (3), Takashi Kaito (2), Noriyuki Tsumaki (1, 7)

Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.Department of Mechanical Systems Engineering, Faculty of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan.
Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Research Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Building 17 Second Floor, 2641, Yamasaki, Noda, Chiba, 278-0042, Japan.
Department of Tissue Biochemistry, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

PubMed

35395453